Phosphorylation-dephosphorylation of proteins is one of the most important mechanisms for the regulation of cellular functions. Protein kinase C, a Ca2+/phospholipid-dependent protein kinase, has emerged as a pivotal regulatory element for cell growth, differentiation, gene expression, hormone secretion, cell surface receptor function, and cellular metabolism. This protein kinase can be activated by diacylglycerol, a second messenger generated by signal-induced breakdown of phosphoinositides. In addition, it has been identified as a receptor for tumor-promoting phorbol esters which elicit pleiotropic responses comparable to those stimulated by many hormones and growth factors. Three isozymic forms of protein kinase C have been identified from rat and monkey brains. Polyclonal and monoclonal antibodies against these enzymes were prepared for their immunochemical characterization. These enzymes were found to have distinct tissue, cellular, and subcellular distributions and were differentially expressed during development. The type 1 protein kinase C, which is expressed only in the central nervous system, was synthesized most actively during synaptogenesis. The content of this enzyme was highest in hippocampus, amygdala, cerebellum, and cerebral cortex. In the cortical regions of the monkey brain visual information processing pathway, the type 1 protein kinase C was found to be high in regions important for memory formation, suggesting its possible role in mnemonic function. The role of each protein kinase C isozyme in cellular regulation was investigated by selecting mutant cell lines deficient in an isozyme. Several type 11 protein kinase C-deficient basophilic leukemia cell lines have been identified. These cell lines will be transfected with the type 11 protein kinase C gene to determine whether physiological responses are modified in the presence and absence of the isoenzyme.